4-oxo-1H-quinoline-2-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-oxo-1H-quinoline-2-carboxylate
• 化学式: C10H6NO3-
• 分子量: 188.16
• InChiKey: HCZHHEIFKROPDY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  AH₂ 、 4-oxo-1H-quinoline-2-carboxylate 、 氧气 生成 7,8-Dihydro-7,8-dihydroxykynurenate 、 A
  参考文献：
  名称：

  TANIUCHI H.; HAYAISHI O., J Biol Chem, 1963, 0021-9258, 283-93

  摘要：

  DOI：
• 作为产物：
  描述：

  4-(2-Aminophenyl)-2,4-dioxobutanoate 生成 水 、 4-oxo-1H-quinoline-2-carboxylate
  参考文献：
  名称：

  Purification and characterization of kynurenine-2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats

  摘要：

  1. 从大鼠的肝脏、大脑和小肠中，使用相同的方法将色氨酸-2-酮戊二酸氨基转移酶（同工酶1）纯化至同质性。三种酶制备物的pH最适值、底物特异性和分子量几乎相同。同工酶1对2-酮戊二酸具有活性，但对丙酮酸没有氨基受体活性，并利用广泛的氨基酸作为氨基供体。氨基酸的活性顺序为：L-天冬氨酸大于L-酪氨酸大于L-苯丙氨酸大于L-色氨酸大于5-羟基-L-色氨酸大于L-犬尿氨酸。通过蔗糖密度梯度离心法测定分子量约为88,000。pH最适值介于8.0和8.5之间。基于底物特异性、底物抑制、亚细胞分布和聚丙烯凝胶电泳，建议肝脏、大脑和小肠色氨酸-2-酮戊二酸氨基转移酶（同工酶1）与线粒体酪氨酸-2-酮戊二酸氨基转移酶以及线粒体天冬氨酸-2-酮戊二酸氨基转移酶相同。2. 从肝脏中另外纯化出一种色氨酸-2-酮戊二酸氨基转移酶（同工酶2）。该酶对2-酮戊二酸和L-犬尿氨酸具有特异性。蔗糖密度梯度离心法测定分子量约为100,000。pH最适值介于6.0和6.5之间。该酶在大脑和小肠中未被检测到。

  DOI：

  10.1042/bj1510399

文献信息

• Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II
  作者：Qian Han、Tao Cai、Danilo A. Tagle、Howard Robinson、Jianyong Li

  DOI：10.1042/bsr20080085

  日期：2008.8.1

  KAT (kynurenine aminotransferase) II is a primary enzyme in the brain for catalysing the transamination of kynurenine to KYNA (kynurenic acid). KYNA is the only known endogenous antagonist of the N-methyl-D-aspartate receptor. The enzyme also catalyses the transamination of aminoadipate to α-oxoadipate; therefore it was initially named AADAT (aminoadipate aminotransferase). As an endotoxin, aminoadipate influences various elements of glutamatergic neurotransmission and kills primary astrocytes in the brain. A number of studies dealing with the biochemical and functional characteristics of this enzyme exist in the literature, but a systematic assessment of KAT II addressing its substrate profile and kinetic properties has not been performed. The present study examines the biochemical and structural characterization of a human KAT II/AADAT. Substrate screening of human KAT II revealed that the enzyme has a very broad substrate specificity, is capable of catalysing the transamination of 16 out of 24 tested amino acids and could utilize all 16 tested α-oxo acids as amino-group acceptors. Kinetic analysis of human KAT II demonstrated its catalytic efficiency for individual amino-group donors and acceptors, providing information as to its preferred substrate affinity. Structural analysis of the human KAT II complex with α-oxoglutaric acid revealed a conformational change of an N-terminal fraction, residues 15–33, that is able to adapt to different substrate sizes, which provides a structural basis for its broad substrate specificity.

  KAT（犬尿氨酸氨基转移酶）Ⅱ是大脑中催化犬尿氨酸转化为 KYNA（犬尿酸）的主要酶。KYNA 是唯一已知的 N-甲基-D-天冬氨酸受体内源性拮抗剂。这种酶还能催化氨基己二酸向α-氧代己二酸的转化，因此最初被命名为 AADAT（氨基己二酸氨基转移酶）。作为一种内毒素，氨基己二酸盐会影响谷氨酸能神经传递的各种因素，并杀死大脑中的原发性星形胶质细胞。文献中有许多关于这种酶的生物化学和功能特性的研究，但尚未对 KAT II 的底物概况和动力学特性进行系统评估。本研究探讨了人 KAT II/AADAT 的生化和结构特征。人 KAT II 的底物筛选显示，该酶具有非常广泛的底物特异性，能够催化 24 种测试氨基酸中 16 种氨基酸的转氨基反应，并能利用所有 16 种测试的 α-氧代酸作为氨基基团接受体。对人类 KAT II 的动力学分析表明了它对单个氨基基团供体和受体的催化效率，从而提供了有关其首选底物亲和性的信息。对人 KAT II 与 α-oxoglutaric acid 复合物的结构分析表明，其 N 端部分残基 15-33 发生了构象变化，能够适应不同大小的底物，这为其广泛的底物特异性提供了结构基础。
• Crystal Structure of Human Kynurenine Aminotransferase I
  作者：Franca Rossi、Qian Han、Junsuo Li、Jianyong Li、Menico Rizzi

  DOI：10.1074/jbc.m409291200

  日期：2004.11

  β-lyase activity toward several sulfur- and selenium-conjugated molecules, leading to the proposal of a role of the enzyme in carcinogenesis associated with environmental pollutants. We solved the structure of human KAT-I in its 5′-pyridoxal phosphate and pyridoxamine phosphate forms and in complex with the competing substrate -Phe. The enzyme active site revealed a striking crown of aromatic residues

  犬尿氨酸途径长期以来一直被认为是治疗几种神经系统疾病的重要靶点，这些疾病伴随着分解代谢级联反应中代谢产物的水平不均衡，其中的运动尿酸是其中之一。犬尿氨酸的不可逆转氨作用是犬尿酸的唯一来源，它是由5'-吡啶氧磷依赖性犬尿氨酸氨基转移酶（KAT）的不同同工型催化的。还已经报道了KAT-1同工酶对几种硫和硒共轭分子具有β-裂合酶活性，从而提出了该酶在与环境污染物有关的致癌作用中的作用的提议。我们解决了人类KAT-1的5'-磷酸吡rid醛和吡ido胺磷酸盐形式，并与竞争性底物1-苯丙氨酸复合的结构。酶的活性位点揭示了一个芳香残基的惊人冠冕，装饰着配体结合袋，我们将其作为底物识别的主要分子决定因素。配体诱导的构象变化影响Tyr（101）和带有Trp（18）的α-螺旋H1似乎在催化中起着核心作用。我们的数据揭示了Glu（27）的关键结构作用，为自发性高血压大鼠KAT-1中等效的Glu-> Gly突变显示的酶活性丧失提供了分子基础。
• Purification and characterization of kynurenine-2-oxoglutarate aminotransferase from the liver, brain and small intestine of rats
  作者：T Noguchi、Y Minatogawa、E Okuno、M Nakatani、M Morimoto、R Kido

  DOI：10.1042/bj1510399

  日期：1975.11.1

  1. Kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) was purified to homogeneity from the liver, brain and small intestine of rats by the same procedure. The three enzyme preparations had nearly identical pH optima, substrate specificities and molecular weights. Isoenzyme 1 was active with 2-oxoglutarate but not with pyruvate as amino acceptor, and utilized a wide range of amino acids as amino donors. Amino acids were effective in the following order to activity: L-aspartate greater than L-tyrosine greater than L-phenylalanine greater than L-tryptophan greater than 5-hydroxy-L-tryptophan greater than L-kynurenine. The molecular weight was approximately 88 000 as determined by sucrose-density-gradient centrifugation. The pH optimum was between 8.0 and 8.5. On the basis of substrate specificity, substrate inhibition, subcellular distribution and polyacrylamide-disc-gel electrophoresis, it is suggested that liver, brain and small intestinal kynurenine-2-oxoglutarate aminotransferase (isoenzyme 1) is identical with mitochondrial tyrosine-2-oxoglutarate aminotransferase and also with mitochondrial aspartate-2-oxoglutarate aminotransferase. 2. An additional kynurenine-2-oxoglutarate aminotransferase (isoenzyme 2) was purified from the liver. This enzyme was specific for 2-oxoglutarate and L-kynurenine. Sucrose-density-gradient centrifugation gave a molecular weight of approximately 100 000. The pH optimum was between 6.0 and 6.5. This enzyme was not detected in the brain or small intestine.

  1. 从大鼠的肝脏、大脑和小肠中，使用相同的方法将色氨酸-2-酮戊二酸氨基转移酶（同工酶1）纯化至同质性。三种酶制备物的pH最适值、底物特异性和分子量几乎相同。同工酶1对2-酮戊二酸具有活性，但对丙酮酸没有氨基受体活性，并利用广泛的氨基酸作为氨基供体。氨基酸的活性顺序为：L-天冬氨酸大于L-酪氨酸大于L-苯丙氨酸大于L-色氨酸大于5-羟基-L-色氨酸大于L-犬尿氨酸。通过蔗糖密度梯度离心法测定分子量约为88,000。pH最适值介于8.0和8.5之间。基于底物特异性、底物抑制、亚细胞分布和聚丙烯凝胶电泳，建议肝脏、大脑和小肠色氨酸-2-酮戊二酸氨基转移酶（同工酶1）与线粒体酪氨酸-2-酮戊二酸氨基转移酶以及线粒体天冬氨酸-2-酮戊二酸氨基转移酶相同。2. 从肝脏中另外纯化出一种色氨酸-2-酮戊二酸氨基转移酶（同工酶2）。该酶对2-酮戊二酸和L-犬尿氨酸具有特异性。蔗糖密度梯度离心法测定分子量约为100,000。pH最适值介于6.0和6.5之间。该酶在大脑和小肠中未被检测到。
• 3-Hydroxykynurenine Transaminase Identity with Alanine Glyoxylate Transaminase
  作者：Qian Han、Jianmin Fang、Jianyong Li

  DOI：10.1074/jbc.m201202200

  日期：2002.5

  This study describes the functional characterization of a specific mosquito transaminase responsible for catalyzing the transamination. of 3-hydroxykynurenine (3-HK) to xanthurenic acid (XA). The enzyme was purified from Aedes aegypti larvae by ammonium sulfate fractionation, heat treatment, and various chromatographic techniques, plus non-denaturing electrophoresis. The purified transaminase has a relative molecular mass of 42,500 by SDS-PAGE. N-terminal and internal sequencing of the purified protein and its tryptic fragments resolved a partial N-terminal sequence of 19 amino acid residues and 3 partial internal peptide sequences with 7, 10, and 7 amino acid residues. Using degenerate primers based on the partial internal sequences for PCR amplification and cDNA library screening, a full-length cDNA clone with a 1,167-bp open reading frame was isolated. Its deduced amino acid sequence consists of 389 amino acid residues with a predicted molecular mass of 43,239 and shares 45-46% sequence identity with mammalian alanine glyoxylate transaminases. Northern analysis shows the active transcription of the enzyme in larvae and developing eggs. Substrate specificity analysis of this mosquito transaminase demonstrates that the enzyme is active with 3-HK, kynurenine, or alanine substrates. The enzyme has greater affinity and catalytic efficiency for 3-HK than for kynurenine and alanine. The biochemical characteristics of the enzyme in conjunction with the profiles of 3-HK transaminase, activity and XA accumulation during mosquito development clearly point out its physiological function in the 3-HK to XA pathway. Our data suggest that the mosquito transaminase was evolved in a manner precisely reflecting the physiological requirement of detoxifying 3-HK produced in the tryptophan oxidation pathway in the mosquito.
• Cysteine and keto acids modulate mosquito kynurenine aminotransferase catalyzed kynurenic acid production
  作者：Qian Han、Jianyong Li

  DOI：10.1016/j.febslet.2004.09.088

  日期：2004.11.19

  Kynurenine aminotransferase (KAT) catalyzes the formation of kynurenic acid (KYNA), the natural antagonist of ionotropic glutamate receptors. This study tests potential substrates and assesses the effects of amino acids and keto acids on the activity of mosquito KAT. Various keto acids, when simultaneously present in the same reaction mixture, display a combined effect on KAT catalyzed KYNA production. Moreover, methionine and glutamine show inhibitory effects on KAT activity, while cysteine functions as either an antagonist or an inhibitor depending on the concentration. Therefore, the overall level of keto acids and cysteine might modulate the KYNA synthesis. Results from this study will be useful in the study of KAT regulation in other animals.